This is an investigation of the pharmacokinetics of salicylate (SA) in infants and children for the purpose of developing safe and effective dosage regimen. The other major emphasis of this investigation is the study of salicylate pharmacokinetics in intoxicated children for the purpose of developing more effective methods of treatment. All significant pharmacokinetic parameters for SA elimination (in vivo KM and Vmax for saturable processes, apparent first-order rate constants for the other, apparent volume of distribution) are being determined as a function of age, body surface area, and disease (incl. unconjugated hyperbilirubinemia, thyroid disorders, inflammatory disease of connective tissue, elevated temperature). Based on this information and on the pronounced pH dependence of the renal clearance of SA, guidelines (incl. nomograms) for rational dosage regimens will be developed, taking into consideration the non-linear nature of SA elimination. Due to the potential hazards of exposing neonates to SA (displacement of bilirubin from plasma proteins resulting in kernicterus), acetaminophen pharmacokinetics will be determined in infants since this mild analgesic-antipyretic appears to be a useful and safe alternative to SA. Another major part of this investigation is concerned with the prevention of salicylate intoxication in infants and children. It includes an assessment of predisposing factors in "therapeutic" intoxications, studies of the pharmacokinetics of peritoneal dialysis, and evaluation of the antidotal effect of activated charcoal as a function of dose, time, and other variables.